PROJECT SUMMARY The central goal of the Wake Forest Translational Alcohol Research Center (WF-TARC) is to employ animal models and human subjects research to study behavioral and neurobiological substrates associated with vulnerability (and resilience) to alcohol use disorder (AUD). This Center builds on a highly productive translational alcohol research program at WFSM that was recently established with NIAAA developmental program project (P01) support. The WF-TARC will have four research projects and two cores. An administrative core will provide the leadership and infrastructure needed to ensure integration across all research projects, provide biostatistical support, and promote interactions and communication between this Center and the many other addiction- related research and educational programs at Wake Forest School of Medicine (WFSM). A pilot project core will be established to advance the goals and objectives of the WF-TARC. This core will fund four projects each year to attract new investigators to bring their talent and expertise to the study of AUD vulnerability. The unifying research focus of the WF-TARC will be to leverage the strengths and advantages of animal models and human subjects research to study behavioral correlates of AUD vulnerability and identify neurobiological adaptations that contribute to this heightened risk of developing AUD. Studies will employ cutting-edge, multidisciplinary experimental approaches spanning molecular, cellular, circuit, and whole-brain analyses. Importantly, each project will evaluate novel interventions targeted at the reversing the maladaptive neural adaptations that promote AUD vulnerability. The highly-integrated conceptual framework and research design will facilitate backward and forward interactions between the projects, facilitating the rapid translation of therapeutic discoveries from animals to humans. The WF-TARC takes advantage of a well-established, extremely collaborative translational alcohol research program at WFSM and will benefit from a strong and growing institutional focus on alcohol and drug addiction research. This Center will further enhance the outstanding educational environment at our institution, providing unique training opportunities for the students and postdoctoral who will become the next generation of translational alcohol researchers. Finally, the innovative research that will be supported by the WF-TARC may lead to better evidence-based therapies for individuals who are at greatest risk of developing AUD, individuals who are particularly ill-served by current AUD treatment options.